The experiments planned involve the use of recently developed in situ optical and electrophysiological techniques to answer specific questions concerning the metabolic effects of certain drugs which act on the central nervous system and by this means to work toward statements about the mechanisms by which some CNS active agents exert their action. Previous work has established some of the relationships between energy metabolism in intact central nervous system and the electrical activity of these tissues in cats. In these investigations, the microfluorometric monitoring technique was used to measure the oxidation-reduction level of intramitochondrial NADH and the technique of reflection spectrophotometry used to measure redox changes in the cytochromes together with changes in hemoglobin oxygenation state and the blood volume. Simultaneous to detection by these non-destructive optical techniques, extracellular potassium levels, steady potential shifts, ECoG and evoked potential activities are monitored on the same tissue areas. By these means, we plan to monitor bioenergetic and electrophysiological functioning in intact, normally circulated CNS areas. Pharmacological agents which have an effect upon the working of the respiratory chain will be monitored and the role of oxygen in these tissues will be considered. In addition, experiments are planned to continue to develop new techniques and preparations to examine the mechanisms by which pharmacological agents alter metabolic and electrical activity near or at the proposed anatomical location of their action. Further work along this line may well yield significant new insights into the energy metabolism of the brain and on the action of CNS drugs.